Field of the Invention
This invention relates to the field of solubility testing of drug compounds and other compounds, and to the field of combinatorial chemistry, and more particularly to the field of micro-solubility testing of drug compounds and other compounds, and to the field of combinatorial chemistry using multi-well reaction blocks for creating new drug compounds. This invention uses a apparatus comprising a disposable device and a reusable instrument that in the case of solubility testing can rapidly mix a solution containing a solvent and a solute, and that can separate the excess solute from the solution to enable testing the solution for solubility. The invention allows this procedure to be performed at a constant temperature. In the case of combinatorial chemistry this invention can rapidly mixes solid phase beads in a solution, and can then separate the solution from the solid phase beads. The invention allows this procedure to be performed at a constant temperature.
At present solubility testing of drug compounds is done by placing the compound (i.e. the solute) in a vial or test tube with a solvent. The vial is capped and the placed on a rocking mechanism in a constant temperature oven, that gently rocks the vial to slowly dissolve the compound into the solvent. At predetermined intervals of time samples are taken from the vial. The samples will contain a solution of solute dissolved in solvent, and some excess solute. The sample must then be filtered to remove the excess solute, so that the solubility can be measured. This method requires a minimum volume of approximately 500 xcexcl and is labor intensive and time consuming.
At present reaction blocks used to synthesize drug compounds are expensive reusable devices, that must be cleaned after each use. The filter frits that are used to separate the drug compound from the solvent must also be replaced after each use. The presently available reusable reaction blocks must be assembled and disassembled several times to synthesize a compound.
The foregoing problems of the prior art are solved, and the objects of the present invention are achieved, by use of the disposable device and reusable instrument constructed in accordance with the principles of the present invention. In accordance with the principles of present invention, the disposable part of the invention includes one or more pairs of chambers, each chamber pair being separated by a filtration means. Each chamber pair includes a first chamber in which a solution is mixed, a filtration means for separating mixed solution from excess solute, and a second chamber that holds the solution less the excess solute. The means for mixing the solution in the first chamber is a rotating magnet. The disposable part of the invention also includes a sealing means that allows the two chambers to be pressurized, and also allows for the removal of a part or all of the solution less excess solute from the second chamber without removing the sealing means.
The reusable part of the invention includes a means to rotate one or more drive magnets; each drive magnet, through its magnetic field, causes one or more follower magnets in the disposable part of the invention to rotate at the same rotational speed as the drive magnet. The follower magnets mix the solution in the one or more first chambers of the disposable part of the invention. Also included in the reusable part of the present invention is a constant temperature water bath for controlling the temperatures of the first and second chambers of the disposable part of the invention. The reusable part of the invention also includes a means to transfer the solution less the excess solute from the first chamber, through the filtration means, to the second chamber, and from the second chamber, through the filtration means, to the first chamber.